P508Human umbilical cord blood-derived mesenchymal stem cells induce vascular endothelial growth in vivo

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Abstract

Purpose

Stem cell therapies represent a hopeful option for cardiac regeneration. Here, we examined both the in vitro and in vivo acquisition of endothelial cell (EC)-specific lineage characteristics by umbilical cord blood-derived mesenchymal stem cells (UCBMSCs).

Methods

Cells were differentiated in the EC-specific growth medium EGM-2. Gene and protein expression were assessed by qRT-PCR, indirect immunofluorescence and Western blotting. In vitro vascular-like network formation was analyzed onto Matrigel. In vivo experiments using co-implantation of Matrigel and UCBMSCs modified for the expression of a human CD31 promoter-regulated luciferase reporter were also carried out in mice. Activation of CD31 promoter was monitored over time using non-invasive bioluminescence, and Matrigel plugs were removed for microvasculature growth analysis following fluorescent angiography. Differentiation response of modified UCBMSCs was finally examined in a mouse model of myocardial infarction (MI).

Results

UCBMSC-derived ECs self organized into vascular-like networks in vitro. Co-implantation of Matrigel and modified UCBMSCs resulted in marked reporter and EC gene activation, and microcirculatory vessel formation as well. Cells embedded in a fibrin patch survived over the infarct area and developed CD31 + vascular-like structures 4 weeks post-implantation. MI-treated animals showed a reduced infarct scar and larger vessel occupied area in comparison with MI-control animals.

Conclusions

Our results show that UCBMSCs contribute to the formation of microcirculatory vessels in vivo, and promote revascularization of ischemic myocardium following acute infarction.

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